crossing96/oncoscreening huggingface dataset:
Nectin-4: a Tumor Cell Target and Status of Inhibitor Development.	PURPOSE OF REVIEW: This study aims to gather the current state of the literature about anti-Nectin-4 innovative associations in solid tumors and to investigate underlying resistance mechanisms. RECENT FINDINGS: Antibody-drug conjugate (ADC) targeting Nectin-4 efficacy gained attention and offers a promising association with other antineoplastic drugs especially in urothelial carcinoma. The heterogeneity of Nectin-4 expression across the molecular subtypes was highlighted especially in urothelial cancers. A unique study using preclinical models demonstrated an upregulation of P-gp expression, which may explain the anti-Nectin-4 resistance mechanisms. Further studies are urgently needed to understand anti-Nectin-4 sensitivity and resistance phenomenon. The growing therapeutic associations of enfortumab vedotin offer optimistic opportunities in management and treatment of wide range of solid tumors including rare aggressive malignancies.	bladder
Differential impact of proton pump inhibitor on survival outcomes of patients with advanced urothelial carcinoma treated with chemotherapy versus pembrolizumab.	OBJECTIVES: We clarified the effect of concomitant proton pump inhibitor use on oncological outcomes in patients with advanced urothelial carcinoma treated either with chemotherapy or immune checkpoint inhibitor. METHODS: We retrospectively reviewed patients with advanced urothelial carcinoma who received paclitaxel-gemcitabine therapy or pembrolizumab after platinum-based chemotherapy. The patients were divided into four groups based on the treatment regimen and the concomitant use of proton pump inhibitor. We compared survival outcomes between the groups and determined which factors predicted overall survival. RESULTS: Among the 60 and 75 patients treated with paclitaxel-gemcitabine and pembrolizumab, 15 and 29 used a concomitant proton pump inhibitor. Progression-free and overall survival was significantly shorter in patients who were administered pembrolizumab with concomitant proton pump inhibitor compared to those without. The use of a concomitant proton pump inhibitor had no effect on survival outcomes in patients who received paclitaxel-gemcitabine therapy. Furthermore, progression-free and overall survival were significantly shorter in patients treated with paclitaxel-gemcitabine therapy compared to those treated with pembrolizumab among patients without concomitant proton pump inhibitor. In contrast, there was no difference in survival outcomes between the two regimens among patients with concomitant proton pump inhibitor. Concomitant proton pump inhibitor use was associated with poor overall survival only in patients treated with pembrolizumab. CONCLUSION: The use of a concomitant proton pump inhibitor use had no impact on oncological outcomes in patients with advanced urothelial carcinoma treated with paclitaxel-gemcitabine therapy, different from those treated with pembrolizumab.	bladder
Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections.	BACKGROUND: BCG is recommended as intravesical immunotherapy to reduce the risk of tumor recurrence in patients with non-muscle invasive bladder cancer (NMIBC). Currently, it is unknown whether intravesical BCG application induces trained immunity. METHODS: The aim of this research was to determine whether BCG immunotherapy induces trained immunity in NMIBC patients. We conducted a prospective observational cohort study in 17 NMIBC patients scheduled for BCG therapy and measured trained immunity parameters at 9 time points before and during a 1-year BCG maintenance regimen. Ex vivo cytokine production by peripheral blood mononuclear cells, epigenetic modifications, and changes in the monocyte transcriptome were measured. The frequency of respiratory infections was investigated in two larger cohorts of BCG-treated and non-BCG treated NMIBC patients as a surrogate measurement of trained immunity. Gene-based association analysis of genetic variants in candidate trained immunity genes and their association with recurrence-free survival and progression-free survival after BCG therapy was performed to investigate the hypothesized link between trained immunity and clinical response. RESULTS: We found that intravesical BCG does induce trained immunity based on an increased production of TNF and IL-1β after heterologous ex vivo stimulation of circulating monocytes 6-12 weeks after intravesical BCG treatment; and a 37% decreased risk (OR 0.63 (95% CI 0.40 to 1.01)) for respiratory infections in BCG-treated versus non-BCG-treated NMIBC patients. An epigenomics approach combining chromatin immuno precipitation-sequencing and RNA-sequencing with in vitro trained immunity experiments identified enhanced inflammasome activity in BCG-treated individuals. Finally, germline variation in genes that affect trained immunity was associated with recurrence and progression after BCG therapy in NMIBC. CONCLUSION: We conclude that BCG immunotherapy induces trained immunity in NMIBC patients and this may account for the protective effects against respiratory infections. The data of our gene-based association analysis suggest that a link between trained immunity and oncological outcome may exist. Future studies should further investigate how trained immunity affects the antitumor immune responses in BCG-treated NMIBC patients.	bladder
Short-Term and Long-Term Morbidity after Radical Cystectomy in Patients with NMIBC and Comparison with MIBC: Identifying Risk Factors for Severe Short-Term Complications.	INTRODUCTION: RC represents a viable treatment option for certain NMIBC patients. However, studies investigating morbidity in the context of RC for NMIBC are scarce. The goal of the current study was to assess and compare morbidity after RC performed in patients with NMIBC and patients with MIBC and to identify risk factors for severe short-term complications. METHODS: Medical records of 521 patients who underwent RC for bladder cancer were retrospectively reviewed. Patients were divided into patients with NMIBC and patients with MIBC. The groups were compared and risk factors for severe complications were identified. RESULTS: RC for NMIBC was performed in 123 patients (23.6%). Histological upstaging was seen in 47 NMIBC patients (38.2%) and in 231 MIBC patients (58%, p < 0.001). OS was 29.8% and CSS was 15.5%. Both endpoints were higher for RC for MIBC (p < 0.001). More complications affecting the urinary diversion were seen with RC for NMIBC (p = 0.033) and more continent urinary diversions (p = 0.040) were performed in those patients. Obesity (p = 0.008), a higher ASA score (p = 0.004), and preoperative medical drug anticoagulation (p = 0.025) were risk factors for severe short-term morbidity after both, RC for NMIBC and for MIBC. CONCLUSION: Patients who underwent RC for NMIBC are exposed to a comparably high perioperative risk than patients with MIBC. RC seems to be a viable treatment option for certain NMIBC patients with a significant histological upstaging in both groups. In patients with obesity, a high ASA score, and with medical drug anticoagulation, the indication for surgery should be confirmed especially strict and possible treatment alternatives should be considered particularly thorough.	bladder
An artificial intelligence model for the pathological diagnosis of invasion depth and histologic grade in bladder cancer.	BACKGROUND: Accurate pathological diagnosis of invasion depth and histologic grade is key for clinical management in patients with bladder cancer (BCa), but it is labour-intensive, experience-dependent and subject to interobserver variability. Here, we aimed to develop a pathological artificial intelligence diagnostic model (PAIDM) for BCa diagnosis. METHODS: A total of 854 whole slide images (WSIs) from 692 patients were included and divided into training and validation sets. The PAIDM was developed using the training set based on the deep learning algorithm ScanNet, and the performance was verified at the patch level in validation set 1 and at the WSI level in validation set 2. An independent validation cohort (validation set 3) was employed to compare the PAIDM and pathologists. Model performance was evaluated using the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: The AUCs of the PAIDM were 0.878 (95% CI 0.875-0.881) at the patch level in validation set 1 and 0.870 (95% CI 0.805-0.923) at the WSI level in validation set 2. In comparing the PAIDM and pathologists, the PAIDM achieved an AUC of 0.847 (95% CI 0.779-0.905), which was non-inferior to the average diagnostic level of pathologists. There was high consistency between the model-predicted and manually annotated areas, improving the PAIDM's interpretability. CONCLUSIONS: We reported an artificial intelligence-based diagnostic model for BCa that performed well in identifying invasion depth and histologic grade. Importantly, the PAIDM performed admirably in patch-level recognition, with a promising application for transurethral resection specimens.	bladder
Quantitative MRI in distinguishing bladder paraganglioma from bladder leiomyoma.	PURPOSE: To investigate the feasibility of quantitative MRI in the differentiation of bladder paraganglioma from bladder leiomyoma. METHODS: From 2014 to 2021, 11 patients with bladder paraganglioma and 14 patients with bladder leiomyoma confirmed by surgical pathology were retrospectively collected. All patients underwent multiparametric scanning with a 3.0 T MR system. Quantitative parameters including the SI-ratio on T(1)WI between the solid component of tumours and piriformis, ADC value and E-rate of the solid component of tumours were assessed. Independent sample t test or Mann-Whitney U test was used to compare these parameters between the two groups. The diagnostic efficiency of the parameters was examined using ROC curve analysis and the DeLong test. RESULTS: There were significant differences in SI-ratio on T(1)WI (P < 0.001), ADC value (P = 0.002) and the E-rate (P = 0.040) between the paraganglioma group and the leiomyoma group. The cutoff value of SI-ratio on 3 leiomyoma was 1.241, and the AUC was 1.000 (0.858-1.000). The cutoff value of the ADC value was 0.979 × 10(-3)mm(2)/s, and the AUC was 0.907 (0.717-0.987). The cutoff value of E-rate was 98.7%, and the AUC was 0.714 (0.495-0.878). The AUCs of the SI-ratio on T(1)WI and ADC value were significantly higher than the E-rate AUC (P = 0.015 and 0.034, respectively). CONCLUSION: Quantitative MRI can effectively distinguish bladder paraganglioma from bladder leiomyoma with the SI-ratio on T(1)WI or ADC value.	bladder
Indications for and results of renal autotransplantation.	PURPOSE OF REVIEW: To understand the indications and outcomes of renal autotransplantation, and when to consider this unique procedure for patients. RECENT FINDINGS: Renal autotransplantation confers acceptably low rates of graft failure and prevents need for long-term dialysis. Renal autotransplantation remains an important management strategy in very select patients for complex renovascular disease, ureteral stricture disease, ureteral trauma, upper urinary tract urothelial carcinoma, renal cell carcinoma, and Loin-Pain Hematuria Syndrome. With advancements in minimally invasive procedures, the application of renal autotransplantation for refractory stone disease is rare but exists. Robot-assisted laparoscopic renal autotransplantation demonstrates reproducible graft success and complication rates with improved perioperative outcomes (ex. hospital length of stay) - though comparative studies are lacking. Patients would benefit from a multidisciplinary approach from renal transplant surgeons, vascular surgeons, urologists, nephrologists, dieticians, pain management providers, social workers, and psychiatrists. SUMMARY: In experienced hands, renal autotransplantation is a reasonable treatment approach for complex and refractory renal vascular disease, Loin-Pain Hematuria Syndrome, ureteral strictures and trauma, upper urinary tract malignancy, and stone disease in highly select patients.	bladder
[STUDY OF URINATION TREATMENT AFTER BCG INTRAVESICAL INSTILLATION THERAPY].	(Background and methods) Bacillus Calmette-Guérin (BCG) intravesical instillation therapy is used to treat non-muscle invasive bladder cancer. Instilled BCG is typically collected at the time of initial urination and disposed of after sterilization with 10% sodium hypochlorite or household bleach, however, these methods can have unpleasant effects, such as pungent odor, rapid foaming and fever. We investigated whether isopropanol be used to sterilize and dispose of urine after BCG intravesical instillation therapy, because isopropanol at a concentration of 33% or higher (70% isopropanol was used in this study) has the same disinfectant and bactericidal effects against Mycobacterium tuberculosis as 10% sodium hypochlorite or household bleach. (Results) Use of isopropanol eliminated the unpleasant effects experienced with sodium hypochlorite and no growth of Mycobacterium tuberculosis was observed in culture tests. (Conclusion) Isopropanol is safer than sodium hypochlorite, and should be considered for sterilizing and disposing of urine after BCG intravesical instillation therapy in the future. However, fire and ventilation precautions are required.	bladder
miRNAs role in bladder cancer pathogenesis and targeted therapy: Signaling pathways interplay - A review.	Bladder cancer (BC) is the 11th most popular cancer in females and 4th in males. A lot of efforts have been exerted to improve BC patients' care. Besides, new approaches have been developed to enhance the efficiency of BC diagnosis, prognosis, therapeutics, and monitoring. MicroRNAs (miRNAs, miRs) are small chain nucleic acids that can regulate wide networks of cellular events. They can inhibit or degrade their target protein-encoding genes. The miRNAs are either downregulated or upregulated in BC due to epigenetic alterations or biogenesis machinery abnormalities. In BC, dysregulation of miRNAs is associated with cell cycle arrest, apoptosis, proliferation, metastasis, treatment resistance, and other activities. A variety of miRNAs have been related to tumor kind, stage, or patient survival. Besides, although new approaches for using miRNAs in the diagnosis, prognosis, and treatment of BC have been developed, it still needs further investigations. In the next words, we illustrate the recent advances in the role of miRNAs in BC aspects. They include the role of miRNAs in BC pathogenesis and therapy. Besides, the clinical applications of miRNAs in BC diagnosis, prognosis, and treatment are also discussed.	bladder
Upper Tract Tumor En Bloc Enucleation: A Novel Approach to the Diagnosis and Management of Upper Tract Urothelial Carcinoma.	OBJECTIVES: To describe and demonstrate our novel en bloc enucleation technique for the endoscopic diagnosis and treatment of upper tract tumors. METHODS: We detail the instruments required for this procedure, as well as the surgical technique to perform an en bloc enucleation and specimen removal. Endoscopic video of a 2 cm renal pelvis tumor demonstrates all aspects of the technique, and histopathologic slides illustrate the diagnostic information obtained. RESULTS: A ureteral access sheath is inserted distal to the upper tract tumor, and a flexible ureteroscope is used to visualize the extent of upper tract disease and tumor characteristics. A 200 μm thulium fiber laser partially ablates the tumor surface to create an edge for tissue biopsy and post-ablation urine cytology. The tumor base is identified and the sub epithelial connective tissue is carefully entered with low ablation laser settings. The correct tissue plane is extended by maintaining the ureteroscope in the subepithelial connective tissue and continuing the dissection along the entire width of the tumor base. Once the tumor is enucleated, a Nitinol stone retrieval basket is used to remove the specimen(s) and a ureteral stent is placed. CONCLUSIONS: En bloc enucleation may provide extensive histopathologic information in upper tract urothelial carcinoma. In cases where complete enucleation is not feasible, this procedure may afford a mechanism for large caliber biopsies.	bladder
Influence of luminal and basal subtype in prognosis of high-grade non muscle invasive urothelial carcinoma.	"BACKGROUND: Recent studies have shown that the classification of high-grade urothelial carcinoma non-muscle invasive (HGBCNMI) based on molecular subtypes might be a valuable strategy to identify patients with a worse clinical prognosis. OBJECTIVE: Determine the effect of the luminal and basal molecular subtype determined by immunistochemical on prognosis in patients with HGBC in Mexican population. METHODS: Phenotypes were evaluated by immunohistochemical staining of luminal (GATA3, FOXA1) and basal (CK5/6, CK14) markers in paraffin-embedded tissue samples from 45 patients with a diagnosis of HGBCNMI treated at Instituto Nacional de Cancerología-México (INCan) between 2009 and 2019. The association with prognosis was evaluated using Kaplan-Meier curves and multivariable-adjusted Cox models. RESULTS: HGBCNMI patients showed mean age of 58.77 years (SD: ±12.08 years). We identified expression of the luminal molecular subtype in 35 cases (77.78 %), and 10 cases (22.22 %) with ""combined"" expression of the molecular subtype (basal and luminal expression). The combined phenotype was statistically more frequent in metastatic cases (p-value = 0.028). In Kaplan-Meier curves, combined expression of luminal and basal molecular markers was associated with disease progression (p-value = 0.002, log-rank test). Cox regression models confirmed this association, which was not influenced by age (p-value = 0.007) or gender (p-value = 0.007). No association of phenotypes with overall survival (p-value = 0.860) or relapse (p-value = 0.5) was observed. CONCLUSION: The combined expression of immunohistochemical markers of the luminal and basal subtype might be considered as predictor for disease progression in patients with HGBCNMI in Mexican population."	bladder
Sea Cucumber Derived Triterpenoid Glycoside Frondoside A: A Potential Anti-Bladder Cancer Drug.	Bladder cancer is a highly recurrent disease and a common cause of cancer-related deaths worldwide. Despite recent developments in diagnosis and therapy, the clinical outcome of bladder cancer remains poor; therefore, novel anti-bladder cancer drugs are urgently needed. Natural bioactive substances extracted from marine organisms such as sea cucumbers, scallops, and sea urchins are believed to have anti-cancer activity with high effectiveness and less toxicity. Frondoside A is a triterpenoid glycoside isolated from sea cucumber, Cucumaria frondosa. It has been demonstrated that Frondoside A exhibits anti-proliferative, anti-invasive, anti-angiogenic, anti-cancer, and potent immunomodulatory effects. In addition, CpG oligodeoxynucleotide (CpG-ODN) has also been shown to have potent anti-cancer effects in various tumors models, such as liver cancer, breast cancer, and bladder cancer. However, very few studies have investigated the effectiveness of Frondoside A against bladder cancer alone or in combination with CpG-ODN. In this study, we first investigated the individual effects of both Frondoside A and CpG-ODN and subsequently studied their combined effects on human bladder cancer cell viability, migration, apoptosis, and cell cycle in vitro, and on tumor growth in nude mice using human bladder cancer cell line UM-UC-3. To interrogate possible synergistic effects, combinations of different concentrations of the two drugs were used. Our data showed that Frondoside A decreased the viability of bladder cancer cells UM-UC-3 in a concentration-dependent manner, and its inhibitory effect on cell viability (2.5 μM) was superior to EPI (10 μM). We also showed that Frondoside A inhibited UM-UC-3 cell migration, affected the distribution of cell cycle and induced cell apoptosis in concentration-dependent manners, which effectively increased the sub-G1 (apoptotic) cell fraction. In addition, we also demonstrated that immunomodulator CpG-ODN could synergistically potentiate the inhibitory effects of Frondoside A on the proliferation and migration of human bladder cancer cell line UM-UC-3. In in vivo experiments, Frondoside A (800 μg/kg/day i.p. for 14 days) alone and in combination with CpG-ODN (1 mg/kg/dose i.p.) significantly decreased the growth of UM-UC-3 tumor xenografts, without any significant toxic side-effects; however, the chemotherapeutic agent EPI caused weight loss in nude mice. Taken together, these findings indicated that Frondoside A in combination with CpG-ODN is a promising therapeutic strategy for bladder cancer.	bladder
Genetic Interference of FGFR3 Impedes Invasion of Upper Tract Urothelial Carcinoma Cells by Alleviating RAS/MAPK Signal Activity.	Upper tract urothelial cancer (UTUC) is a less common disease in Western countries but has a high level of prevalence in Asian populations. Compared to bladder cancer, unique etiologic and genomic factors are involved in UTUC. Fibroblast growth factor receptor 3 (FGFR3) up-regulation has been proposed as a promising target for bladder cancer therapy. In this study, we aimed to profile the expression of FGFR3 in Asian and Caucasian UTUC tissues and to evaluate the in vitro therapeutic efficacy of small interference RNA (siRNA)-mediated FGFR3 silencing in UTUC treatment. The FGFR3 expression levels in renal pelvis tissues and microarray sections from Asian and Caucasian patients with UTUC, respectively, were measured via immunohistochemistry. The BFTC-909 and UM-UC-14 UTUC cell lines were used to examine the effects of FGFR3 silencing on proliferation, migration, epithelial-mesenchymal transition (EMT) marker expression, and signaling machinery. FGFR3 expression increased as the TNM stage increased in both Asian and Caucasian UTUC tumors, and no statistical difference was identified between the two groups. In vitro studies demonstrated that FGFR3 siRNA delivery significantly inhibited proliferation and migration and suppressed the expression of EMT markers and transcription factors in UTUC cells. Mechanistically, FGFR3 silencing alleviated the constitutive expression of RAS and the phosphorylation of MAPK signaling mediators, including ERK1/2 and JNK1/2. FGFR3 silencing elicited an apoptosis-inducing effect similar to that of FGFR inhibition. Conclusion: siRNA-targeted FGFR3 expression may impede the expansion and invasion of UTUC cells by alleviating the RAS/MAPK signaling pathway. The genetic interference of FGFR3 expression via siRNA in UTUC cells may constitute a useful therapeutic strategy.	bladder